Search results for "death"
showing 10 items of 1744 documents
Novel isatin-derived molecules activate p53 via interference with Mdm2 to promote apoptosis
2018
International audience; The p53 protein is a key tumor suppressor in mammals. In response to various forms of genotoxic stress p53 stimulates expression of genes whose products induce cell cycle arrest and/or apoptosis. An E3-ubiquitin ligase, Mdm2 (mouse-double-minute 2) and its human ortholog Hdm2, physically interact with the amino-terminus of p53 to mediate its ubiquitin-mediated degradation via the proteasome. Thus, pharmacological inhibition of the p53-Mdm2 interaction leads to overall stabilization of p53 and stimulation of its anti-tumorigenic activity. In this study we characterize the biological effects of a novel class of non-genotoxic isatin Schiff and Mannich base derivatives (…
High dose infusion of activated protein C (rhAPC) fails to improve neuronal damage and cognitive deficit after global cerebral ischemia in rats
2013
Abstract Purpose : Recent studies demonstrated anticoagulatory, antiinflammatory, antiapoptotic, and neuroprotective properties of activated protein C (APC) in rodent models of acute neurodegenerative diseases, suggesting APC as promising broad acting therapeutic agent. Unfortunately, continuous infusion of recombinant human APC (rhAPC) failed to improve brain damage following cardiac arrest in rats. The present study was designed to investigate the neuroprotective effect after global cerebral ischemia (GI) with an optimized infusion protocol. Methods : Rats were subjected to bilateral clip occlusion of the common carotid arteries (BCAO) and controlled hemorrhagic hypotension to 40 mmHg for…
Job in Literature
1997
This classic counsel of despair is uttered by Job’s wife in the wake of all the evils which befall him (Job 2:9). It is preceded by the question, ‘Dost thou still retain thine integrity?’ Her words may have been motivated by bitterness over what she and Job had endured (the Septuagint and the apocryphal Testament of Job both give her a lengthy speech in which she catalogues their degradation). Possibly she felt that blasphemy would have sudden death as a consequence, and that this would put Job out of his misery. In any case, the import of her words is to question the value of ‘righteousness’ (cf. Tobit 2:11–14).
Pancreatitis aguda necrótico-hemorrágica: propósito de dos autopsias judiciales
2015
la pancreatitis necrótico-hemorrágica, es una complicación inusual y altamente mortal en los casos de inflamación de la glándula pancreática. El diagnóstico es de sospecha clínica apoyado por pruebas de laboratorio y de radiodiagnóstico. Constituye una causa excepcional de muerte súbita. Pero esta forma de presentación de pancreatitis sólo puede ser confirmada mediante el estudio anatomopatológico de la glándula, del cual se dispone en raras ocasiones. Exponemos los hallazgos macroscópicos de dos casos mortales de Pancreatitis Aguda Necro-Hemorrágica. hemorrhagic and necrotizing pancreatitis, is an unusual and highly lethal complication in cases of inflammation of the pancreatic gland. The …
Regulation of X Chromosome-Linked Inhibitor of Apoptosis Protein (XIAP) in Kainic Acid Induced Neuronal Cell Death in the Rat Hippocampus
2001
INTRODUCTION. Inhibitor of apoptosis protein (IAP) family consists of several antiapoptotic proteins conserved among species. The IAPs have a well-conserved motif of approximately 65 residues, called the baculovirus inhibitory repeat (BIR) (1). Baculovirus and drosophila IAPs have two, but most IAPs contain three BIR domains. Most of the IAPs also have a C-terminal RING domain which consists of conserved amino acids with zinc binding capacity. XIAP is one of the five known human IAPs and it binds directly and inhibits the activity of caspases (2). The BIR2 domain in XIAP is sufficient to mediate this inhibition (3). However little is known about the presence and function of XIAP in the nerv…
cFLIPL Inhibits Tumor Necrosis Factor-related Apoptosis-inducing Ligand-mediated NF-κB Activation at the Death-inducing Signaling Complex in Human Ke…
2004
Human keratinocytes undergo apoptosis following treatment with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) via surface-expressed TRAIL receptors 1 and 2. In addition, TRAIL triggers nonapoptotic signaling pathways including activation of the transcription factor NF-kappaB, in particular when TRAIL-induced apoptosis is blocked. The intracellular protein cFLIP(L) interferes with TRAIL-induced apoptosis at the death-inducing signaling complex (DISC) in many cell types. To study the role of cFLIP(L) in TRAIL signaling, we established stable HaCaT keratinocyte cell lines expressing varying levels of cFLIP(L). Functional analysis revealed that relative cFLIP(L) levels correlat…
Differential role of p38 mitogen activated protein kinase for cellular recovery from attack by pore-forming S. aureus alpha-toxin or streptolysin O.
2006
Following the observation that cells are able to recover from membrane lesions incurred by Staphylococcus aureus alpha-toxin and streptolysin O (SLO), we investigated the role of p38 in this process. p38 phosphorylation occurred in response to attack by both toxins, commencing within minutes after toxin treatment and waning after several hours. While SLO reportedly activates p38 via ASK1 and ROS, we show that this pathway does not play a major role for p38 induction in alpha-toxin-treated cells. Strikingly divergent effects of p38 blockade were noted depending on the toxin employed. In the case of alpha-toxin, inhibition of p38 within the time frame of its activation led to disruption of th…
Staphylococcal alpha-toxin kills human keratinocytes by permeabilizing the plasma membrane for monovalent ions
1993
Incubation of human keratinocytes with nanomolar concentrations of Staphylococcus aureus alpha-toxin leads to irreversible depletion of cellular ATP. The toxin forms hexamers in the target cell membranes, and rapid transmembrane flux of K+, Na+, and 86Rb+ is observed. Unexpectedly, pores formed in keratinocytes through application of low but lethal doses of alpha-toxin appeared to be considerably smaller than those formed in erythrocyte membranes. They permitted neither rapid influx of Ca2+ or propidium iodide, nor efflux of carboxyfluorescein. Larger pores allowing flux of all three markers did form when the toxin was applied at high concentrations. Flux of monovalent ions and reduction in…
Early and midterm outcomes of bioresorbable vascular scaffolds for ostial coronary lesions: insights from the GHOST-EU registry.
2016
Aims: We aimed to investigate the outcomes of bioresorbable vascular scaffolds (BVS) in coronary ostial lesions. Ostial lesions represent a challenging angiographic subset, with higher event rates compared with non-ostial lesions. BVS might be associated with advantages over the long term, but their safety in this setting remains to be explored. Methods and results: Procedural and 12-month follow-up data from consecutive patients treated with BVS for lesions located at the ostium of the right (RCA), left anterior (LAD) or circumflex (LCX) coronary in 11 European centres were collected. The primary device-oriented endpoint was defined as a combination of cardiovascular death, target vessel m…
« Lee Miller, War “ethical” Photographer?»
2013
International audience; This presentation discusses some of Lee Miller photographs of Dachau and argues of their ethical relevance.